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Oncotarget. 2016 Aug 9;7(32):51608-51618. doi: 10.18632/oncotarget.9958.

Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice.

Author information

1
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
2
School of Medicine, Tzu Chi University, Hualien, Taiwan.
3
Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
4
Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan.
5
Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
6
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
7
Department of Biotechnology, Asia University, Taichung, Taiwan.
8
China Medical University Hospital, China Medical University, Taichung, Taiwan.

Abstract

Cancer cachexia is characterized by anorexia, skeletal muscle atrophy, and systemic inflammation. Fucoidan extracted from brown algae exhibits anti-inflammatory and anticancer activities. However, whether fucoidan ameliorates tumour and chemotherapy-induced muscle atrophy and -related cachectic symptoms remains unknown. Compared with mice with bladder cancer treated with chemotherapy alone (TGC group), those treated with a combination of low molecular weight fucoidan (LMWF) and chemotherapy drugs such as gemcitabine and cisplatin (TGCF) showed a significant reduction of body weight loss, muscle atrophy, and intestinal injury and dysfunction. Moreover, myostatin, activin A, and pro-inflammatory cytokine production, FoxO3 expression and activation, NF-κB activation, MuRF-1 and MAFbx/atrogin-1 expression, and proteasome activity in muscle were significantly decreased in the TGCF group compared with the TGC group. In addition, insulin-like growth factor 1 (IGF-1) expression and formation, and IGF-1-regulated mTOR/p70S6k/4EBP-1 protein synthesis signalling were elevated in the TGCF group compared with the TGC group. Taken together, these results suggest that LMWF is a potential agent for preventing cancer cachexia-associated muscle atrophy during chemotherapy. Furthermore, the beneficial effect of LMWF may be attributed to suppressing NF-κB-evoked inflammation, myostatin and activin A production, and subsequent muscle proteolysis, and enhancing IGF-1-dependent protein synthesis.

KEYWORDS:

cancer cachexia; chemotherapy; fucoidan; inflammation; muscle atrophy

PMID:
27323407
PMCID:
PMC5239500
DOI:
10.18632/oncotarget.9958
[Indexed for MEDLINE]
Free PMC Article

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